There exists, in mammals, polypeptides belonging to the tachykinin family that induce rapid contractions on smooth muscle fibres. Among the compounds of this family, mention may be made of neurokinin-β, neurokinin-α and substance P.
Substance P is a polypeptide (undecapeptide) chemical element produced and released by a nerve ending. The location of substance P is neurone-specific, both in the central nervous system and in peripheral organs. Thus, a very large number of organs or tissues receive substance P neuron afferences; they are, in particular, salivary glands, the stomach, the pancreas, the intestine (in the latter, the distribution of substance P is superimposed with Meissner's and Auerbach's intrinsic nerve plexuses), the cardiovascular system, the thyroid gland, the skin, the iris and the ciliary bodies, the bladder and, of course, the central and peripheral nervous systems.
By virtue of the ubiquitous distribution of substance P, numerous disorders are associated with an excess synthesis and/or release of substance P.
Substance P is in particular involved in the transmission of pain and in central nervous system diseases (for example, anxiety, psychoses, neuropathies, neurodegenerative conditions such as Alzheimer's senile dementia, age-related dementia, Parkinson's disease, Down's syndrome, Korsakoff's syndrome, multiple sclerosis, schizophrenia), in respiratory diseases (such as, for example, bronchial pneumonia) and inflammatory diseases (such as, for example, rheumatoid arthritis), in allergic syndromes (such as, for example, asthma, allergic rhinitis, allergic pharyngitis, urticaria, eczematous dermatitis), in gastrointestinal diseases (such as, for example, ulcers, colitis, Crohn's disease), in skin disorders (such as, for example, rosacea, psoriasis, pruriginous diseases, herpes, photodermatoses, atopic dermatitis, contact dermatitis, lichens, pruritis, prurigo, erythema, in particular solar erythema, insect bites), in fibroses and other conditions of collagen maturation (such as, for example, scleroderma), in cardiovascular conditions, vasospastic conditions (such as, for example, migraines, Reynaud's disease), in immunological disorders, in urinary tract conditions (such as, for example, incontinence, cystitis), in rheumatic diseases, in certain dermatological diseases (such as eczema) and in ophthalmological conditions (such as, for example, conjunctivitis, uveitis, ocular pruritis, ocular pain, irritations).
More specifically, when it is released in the skin, substance P exerts a vasodilatation and a plasma extravasation that can induce redness of the skin and oedema.
The use of a substance P antagonist is an effective means of preventing and/or reducing and/or treating the manifestations mentioned above.
The term “substance P antagonist” as used herein is intended to mean any compound capable of partially, or even totally, inhibiting the biological effect of substance P. In particular, for a substance to be recognized as a substance P antagonist, it must induce a coherent pharmacological response (possibly including its binding to the substance P receptor), for example in one of the following tests:                the antagonist substance must decrease plasma extravasation through the vascular wall induced by capsaicin or by an antidromic nerve stimulation, or else        the antagonist substance must cause an inhibition of the smooth muscle contraction induced by the administration of substance P.        
It has also been demonstrated that substance P may be responsible for skin manifestations that characterize sensitive skin; the term “skin” is intended to mean any cutaneous surface of the body including the scalp.
In general, sensitive skin is defined by a specific reactivity of the skin. This skin reactivity is conventionally reflected by the manifestation of signs of discomfort in response to the individual coming into contact with a triggering element which may have various origins. It may be the application of a cosmetic product to the surface of the sensitive skin, the ingestion of food products, exposure to abrupt temperature variations, to atmospheric pollution and/or to ultraviolet or infrared rays. Related factors such as age and skin type also exist. Thus, sensitive skin is more common among dry or greasy skin than among normal skin.
The appearance of these signs of discomfort, which appear within minutes following the individual coming into contact with the triggering element, is one of the essential characteristics of sensitive skin. They involve mainly dysaesthesic sensations. The term “dysaesthesic sensations” is intended to mean more or less painful sensations felt in an area of skin, such as stinging, pins and needles, itching, burning, overheating, discomfort, tautness, etc. These subjective signs most commonly exist in the absence of visible clinical signs such as redness and desquamations. It is today known that these skin intolerance and irritation reactions are in particular related to a release of neuropeptides by the epidermal and dermal nerve endings.
In contrast with skin described as allergic, the reactivity of sensitive skin is not the result of an immunological process. Its response mechanism is termed “aspecific”. It is, in this respect, to be distinguished from skin that shows inflammatory and allergic reactions of dermatosis, eczema and/or ichtyosis type, and with respect to which a certain number of treatments have already been proposed.
For obvious reasons, the absence of visible signs makes it difficult to diagnose sensitive skin. Most commonly, this diagnoses is based on questioning the patient. This symptomatology also has the advantage of making it possible to differentiate sensitive skin from contact irritation or allergy for which, on the other hand, visible inflammatory signs exist.
Consequently, the development of “sensitive skin” products has required the provision of tools for evaluating the sensorial reaction of the skin. The inspiration for the first tools, starting with their design, came from the essential characteristic of sensitive skin, namely the presence of signs of discomfort induced by a topical application.
Thus, the lactic acid “stinging test” was the first test proposed. It is carried out by recording stinging sensations reported by a volunteer after application of a 10% lactic acid solution to the sides of the nose. Individuals reporting moderate or strong stinging sensations are called “stingers” and are considered to have sensitive skin. Because of this sensitivity of the skin to the topical application of a product, these individuals are than selected for testing “sensitive skin” products. More recently, in order to specifically activate the peripheral nerve endings involved in discomfort, and called nociceptors, recently identified as being involved in sensitive skin, new tests have been proposed that in fact use other inducers of discomfort such as capsaicin.
This second type of test, described in application EP 1 374 913, also constitutes another particularly useful means for the diagnosis of sensitive skin.
For the purpose of the present invention, sensitive skin can cover irritable skin and intolerant skin. Intolerant skin is skin that reacts to various factors, such as the application of cosmetic or dermatological products or soap, through sensations of overheating, tautness, pins and needles and/or redness. In general, these signs are associated with erythema and with hyperseborrheic or acneic skin, or even skin exhibiting rosacea, with or without sores.lrritable skin is skin that reacts through pruritus, i.e. through itching or stinging, to various factors such as the environment, emotions, foods, the wind, rubbing, shaving, hard water with a high calcium concentration, temperature variations, humidity or wool.
“Sensitive” scalps have a more unambiguous clinical semiology: the itching and/or stinging and/or overheating sensations are essentially triggered by local factors such as rubbing, soap, surfactants, hard water with a high calcium concentration, shampoos or lotions. These sensations are also sometimes triggered by factors such as the environment, emotions and/or foods. An erythema and hyperseborrhae of the scalp and also dandruff are frequently associated with the above signs.